Neoplasms

All Conditions

Symptoms and General Pathology

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Rare Diseases

Adenocarcinoma

Weight Loss

Body Weight

Hyperplasia

Endometrial Hyperplasia

Uterine Neoplasms

Carcinoma

Carcinoma, Endometrioid

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Endometrial Neoplasms

Genital Neoplasms, Female

Urogenital Neoplasms

Ovarian Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Gonadal Disorders

Endocrine System Diseases

Uterine Diseases

Ovarian Cancer

Hypoglycemic Agents

All Drugs and Chemicals

Reproductive Control Agents

Metformin

Levonorgestrel

Contraceptive Agents

Contraceptive Agents, Hormonal

Contraceptive Agents, Female

Contraceptives, Oral

Metformin tablets, 500mg twice daily orally, 6 months Levonorgestrel (Mirena®) 52mg Intrauterine drug delivery system, 6 months

Levonorgestrel (Mirena®) 52mg Intrauterine drug delivery system, 6 months

Levonorgestrel (Mirena®) 52mg Intrauterine drug delivery system, 6 months Weight Loss Intervention will be delivered via Weight Watchers

Andreas Obermair

Currently the standard treatment for early stage endometrial cancer or endometrial hyperplasia with atypia is a total hysterectomy (an operation to remove the uterus) and removal of both ovaries. While highly effective, this surgery carries significant side effects for:

* young women who still wish to have children and would lose fertility; and
* women with one or more disorders (or diseases) in addition to the early stage endometrial cancer or endometrial hyperplasia with atypia and/or morbid obesity who are at risk for surgical complications making surgery unsafe.

This study will access a new approach to the treatment of endometrial cancer to spare women of having to undergo major surgery that may be unwanted or unnecessary.

Mirena is approved in Australia for contraception, to treat heavy bleeding, and to prevent thickening of the lining of the uterus (endometrial hyperplasia) during oestrogen replacement therapy (HRT). However it is not approved to treat early stage endometrial cancer or endometrial hyperplasia with atypia. This research project will test to see if Mirena is an effective treatment for early stage endometrial cancer and endometrial hyperplasia with atypia.

Metformin is approved in Australia to treat Diabetes. However it is not approved to treat early stage endometrial cancer or endometrial hyperplasia with atypia. Therefore, it is an experimental treatment for early stage endometrial cancer and endometrial hyperplasia with atypia. This means that it must be tested to see if it is an effective treatment for early stage endometrial cancer and endometrial hyperplasia with atypia.

Weight loss interventions are feasible and safe, and already being implemented by gynaecologic oncologist to make women eligible for surgery. Weight loss of 7% body weight induces a large biological effect (for example reduces incidence of diabetes by 58%, and hypertension by 26%).

Improving the Treatment for Women With Early Stage Cancer of the Uterus

A Phase II Randomised Clinical Trial of Mirena® ± Metformin ± Weight Loss Intervention in Patients With Early Stage Cancer of the Endometrium

To predict the response to treatment through blood and tissue molecular biomarkers and to increase our molecular understanding of the biological pathogenesis of "early" EAC.

The University of Queensland

Queensland University of Technology

Queensland Centre for Gynaecological Cancer

Carcinoma, Ovarian Epithelial

Endocrine Gland Neoplasms

Ovarian Epithelial Cancer

Norgestrel

Contraceptives, Oral, Hormonal

Patients receive oral levonorgestrel once daily.

Patients receive oral placebo once daily.

Laboratory Biomarker Analysis

Placebo

Gustavo C Rodriguez

This randomized phase II trial is studying how well levonorgestrel works in preventing ovarian cancer in patients at high risk for ovarian cancer. Chemoprevention is the use of certain drugs to keep cancer from forming. The use of levonorgestrel may prevent ovarian cancer.

PRIMARY OBJECTIVES:

I. Determine the impact of levonorgestrel on the relative frequency of apoptosis in the ovarian epithelium of patients at high risk for ovarian cancer.

SECONDARY OBJECTIVES:

I. Estimate the impact of this drug on proliferation and transforming growth factor-beta (TGF-beta) expression in the ovarian epithelium of these patients.

II. Assess the safety of this drug in these patients.

OUTLINE: This is a prospective, randomized, placebo-controlled, double-blind study. Patients are stratified according to menopausal status (premenopausal vs postmenopausal). Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive oral levonorgestrel once daily.

ARM II: Patients receive oral placebo once daily.

In both arms, treatment continues for 4-6 weeks in the absence of disease progression or unacceptable toxicity, including on the day of surgery. Patients then undergo prophylactic salpingo-oophorectomy. After completion of study therapy, patients are followed at 1 year.

NOTE: \* Patients who are unable to have surgery completed during the expected 4-6 weeks, may continue levonorgestrel or placebo for a time period no \> 5 months. Patients unable to undergo surgery within 5 months are removed from the study.

Levonorgestrel in Preventing Ovarian Cancer in Patients at High Risk for Ovarian Cancer

Phase II Double Blind Randomized Trial Evaluating the Biologic Effect of Levonorgestrel on the Double Blind Randomized Trial Evaluating the Biologic Effect of Levonorgestrel on the Ovarian Epithelium in Women at High Risk for Ovarian Cancer

The median proportion of cells that are considered to be apoptotic are counted in the fallopian tube tissue sample, among the total number of cells available in the sample slide

The median proportion of cells that are considered to be apoptotic are counted in the ovarian tissue sample, among the total number of cells available in the sample slide.

Participants were graded using CTCAE v.30 criteria. Grade 1 is the least severe grade. Each adverse event lists criteria for grading, grade 1 being mild, up to grade 5. Grade 4 is generally life threatening. Grade 5 is death.

National Cancer Institute (NCI)

Gynecologic Oncology Group

Levenorgestrel (0.15 mg/day) for 4 to 6 weeks for 4 to 6 weeks

Arm I (Levenorgestrel)

Arm II (Placebo)

Total

20-29 years

30-39 years

40-49 years

50-59 years

60-69 years

Age, Customized

Sex: Female, Male

Linda Gedeon for James Kauderer, MA

Patients with evaluable slides. 14 of the cases did not have ovarian tissue available for evaluation. 50 cases were available for the primary analysis.

Median Proportion Cells That Are Apoptotic in Epithelial Ovarian Tissue

Allergy/Immunology

Constitutional Symptoms

Cardiac

Dermatology/Skin

Endocrine

Gastrointestinal

Renal/Genitourinary

Hemorrhage/Bleeding

Blood/Bone Marrow

Infection

Metabolic/Laboratory

Neurology

Pulmonary/Upper Respiratory

Pain

Sexual/Reproductive Function

Number of patients on arm 1 who experienced a grade 1 event using CTCAE v 3.0

Grade 1 CTCAE v 3.0 Arm I (Levonorgestrel)

Number of patients on arm 1 who experienced a grade 2 event using CTCAE v 3.0

Grade 2 CTCAE v 3.0 Arm 1 (Levonorgestrel)

Number of patients on arm 1 who experienced a grade 3 event using CTCAE v 3.0

Grade 3 CTCAE v 3.0 Arm 1 (Levonorgestrel)

Number of patients on arm ! who experienced a grade 4 event using CTCAE v. 3.0

Grade 4 CTCAE v3.0 Arm 1 Levonorgestrel)

Number of patients on arm I who experienced a grade 5 event using CTCAE v. 3.0

Grade 5 CTCAE v3.0 Arm I (Levonorgestrel)

Number of patients on arm II who experienced a grade 1 event using CTCAE v.30

Grade 1 CTCAE 3.0 Arm II (Placebo)

Number of patients on arm II who experienced a grade 2 event using CTCAE 3.0

Grade 2 CTCAE 3.0 Arm II (Placebo)

Number of patients on arm II who experienced a grade 3 event using CTCAE 3.0

Grade 3 CTCAE 3.0 Arm II (Placebo)

Number of patients on arm II who experienced a grade 4 event using CTCAE 3.0

Grade 4 CTCAE 3.0 Arm II (Placebo)

Number of patients on arm II who experienced a grade 5 event using CTCAE 3.0

Grade 5 CTCAE 3.0 Arm II (Placebo)

All eligible and treated patients who had toxicity on study.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Improving the Treatment for Women With Early Stage Cancer of the Uterus	NCT01686126	Complex Endomet... Grade 1 Endomet...	Levonorgestrel Metformin	18 Years -	Queensland Centre for Gynaecological Cancer
Levonorgestrel in Preventing Ovarian Cancer in Patients at High Risk for Ovarian Cancer	NCT00445887	Ovarian Carcino...	Laboratory Biom... Levonorgestrel Placebo	30 Years -	GOG Foundation

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